Title:
PYRAZOLO[3,4-D]PYRIMIDINES AS SFK INHIBITORS
Document Type and Number:
WIPO Patent Application WO/2016/066755
Kind Code:
A3
Abstract:
The present invention refers to 4-amino-substituted pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine derivatives of formula I and IV able to target the Src family kinases (SFKs) such as Src, Fyn and Hck tyrosine kinases as well as Abl tyrosine kinase and uses and method of preparation thereof. In particular, the compounds of the invention are for use in the treatment and/or prevention of cancer, such as neuroblastoma (NB) or glioblastoma multiforme (GBM) or for use in the treatment and/or prevention of neurodegenerative diseases such as taupathies.
Inventors:
BOTTA MAURIZIO (IT)
ANGELUCCI ADRIANO (IT)
DREASSI ELENA (IT)
SCHENONE SILVIA (IT)
TINTORI CRISTINA (IT)
VIGNAROLI GIULIA (IT)
ANGELUCCI ADRIANO (IT)
DREASSI ELENA (IT)
SCHENONE SILVIA (IT)
TINTORI CRISTINA (IT)
VIGNAROLI GIULIA (IT)
Application Number:
PCT/EP2015/075148
Publication Date:
June 23, 2016
Filing Date:
October 29, 2015
Export Citation:
Assignee:
LEAD DISCOVERY SIENA S R L (IT)
International Classes:
C07D487/04; A61K31/519; A61K31/5377; A61P25/00; A61P35/00
Domestic Patent References:
| WO2009034547A2 | 2009-03-19 | |||
| WO2011014239A1 | 2011-02-03 |
Other References:
GUO HUA ZENG ET AL: "Theoretical Studies on Pyrazolo[3,4- d ]pyrimidine Derivatives as Potent Dual c-Src/Abl Inhibitors Using 3D-QSAR and Docking Approaches", MOLECULAR INFORMATICS, vol. 33, no. 3, 11 March 2014 (2014-03-11), pages 183 - 200, XP055181223, ISSN: 1868-1743, DOI: 10.1002/minf.201300126
MARIA ALESSANDRA SANTUCCI ET AL: "C6-Unsubstituted Pyrazolo[3,4- d ]pyrimidines Are Dual Src/Abl Inhibitors Effective against Imatinib Mesylate Resistant Chronic Myeloid Leukemia Cell Lines", CHEMMEDCHEM, vol. 4, no. 1, 12 January 2009 (2009-01-12), pages 118 - 126, XP055181226, ISSN: 1860-7179, DOI: 10.1002/cmdc.200800320
NAVARRA MICHELE ET AL: "Antiproliferative and pro-apoptotic effects afforded by novel Src-kinase inhibitors in human neuroblastoma cells", BMC CANCER, BIOMED CENTRAL, LONDON, GB, vol. 10, no. 1, 4 November 2010 (2010-11-04), pages 602, XP021075425, ISSN: 1471-2407, DOI: 10.1186/1471-2407-10-602
MARCO RADI ET AL: "Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4- d ]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, no. 8, 28 April 2011 (2011-04-28), pages 2610 - 2626, XP055181295, ISSN: 0022-2623, DOI: 10.1021/jm1012819
GIULIA VIGNAROLI ET AL: "Exploring the Chemical Space around the Privileged Pyrazolo[3,4- d ]pyrimidine Scaffold: Toward Novel Allosteric Inhibitors of T315I-Mutated Abl", ACS COMBINATORIAL SCIENCE, vol. 16, no. 4, 14 April 2014 (2014-04-14), pages 168 - 175, XP055155165, ISSN: 2156-8952, DOI: 10.1021/co500004e
CHAUHAN MONIKA ET AL: "Medicinal attributes of pyrazolo[3,4-d]pyrimidines: A review", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 21, no. 18, 20 July 2013 (2013-07-20) - 20 July 2013 (2013-07-20), pages 5657 - 5668, XP028693350, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2013.07.027
MARIA ALESSANDRA SANTUCCI ET AL: "C6-Unsubstituted Pyrazolo[3,4- d ]pyrimidines Are Dual Src/Abl Inhibitors Effective against Imatinib Mesylate Resistant Chronic Myeloid Leukemia Cell Lines", CHEMMEDCHEM, vol. 4, no. 1, 12 January 2009 (2009-01-12), pages 118 - 126, XP055181226, ISSN: 1860-7179, DOI: 10.1002/cmdc.200800320
NAVARRA MICHELE ET AL: "Antiproliferative and pro-apoptotic effects afforded by novel Src-kinase inhibitors in human neuroblastoma cells", BMC CANCER, BIOMED CENTRAL, LONDON, GB, vol. 10, no. 1, 4 November 2010 (2010-11-04), pages 602, XP021075425, ISSN: 1471-2407, DOI: 10.1186/1471-2407-10-602
MARCO RADI ET AL: "Design, Synthesis, Biological Activity, and ADME Properties of Pyrazolo[3,4- d ]pyrimidines Active in Hypoxic Human Leukemia Cells: A Lead Optimization Study", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, no. 8, 28 April 2011 (2011-04-28), pages 2610 - 2626, XP055181295, ISSN: 0022-2623, DOI: 10.1021/jm1012819
GIULIA VIGNAROLI ET AL: "Exploring the Chemical Space around the Privileged Pyrazolo[3,4- d ]pyrimidine Scaffold: Toward Novel Allosteric Inhibitors of T315I-Mutated Abl", ACS COMBINATORIAL SCIENCE, vol. 16, no. 4, 14 April 2014 (2014-04-14), pages 168 - 175, XP055155165, ISSN: 2156-8952, DOI: 10.1021/co500004e
CHAUHAN MONIKA ET AL: "Medicinal attributes of pyrazolo[3,4-d]pyrimidines: A review", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 21, no. 18, 20 July 2013 (2013-07-20) - 20 July 2013 (2013-07-20), pages 5657 - 5668, XP028693350, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2013.07.027
Attorney, Agent or Firm:
CAPASSO, Olga et al. (Via Vincenzo Bellini 20, Rome, IT)
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